Combined Modality Targeted Therapy of Pancreatic Cancer with Death Receptor
Combined Modality Targeted Therapy of Pancreatic Cancer with Death Receptor
批准号:
7962128
负责人:
DONALD J. BUCHSBAUM
金额:
$18.36万
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-03-01 至 2015-02-28
关键词:
AccountingAdaptor Signaling ProteinAddressAdvanced Malignant NeoplasmAdverse effectsAgonistAmerican Society of Clinical OncologyAnimal ModelAntibodiesApoptosisApoptosis InhibitorAttentionBiological MarkersBiologyCancer CenterCancer ModelCancer PatientCancer cell lineCaspaseCell DeathCell LineCell surfaceCessation of lifeClinicalClinical TrialsCombined Modality TherapyComplexCredentialingDataDeath DomainDevelopmentDiseaseDisseminated Malignant NeoplasmDoctor of MedicineDoseEnrollmentEpidermal Growth Factor ReceptorEvaluationExhibitsExternal Beam Radiation TherapyFamilyFundingFutureGoalsGrantHepatocyteHumanHuman GenomeIn VitroInduction of ApoptosisInstructionLeadLicensingLigandsLiteratureMalignant NeoplasmsMalignant neoplasm of pancreasManuscriptsMediatingMembraneMinnesotaModalityModelingMolecularMolecular ProfilingMonoclonal AntibodiesMonoclonal Antibody C225Monoclonal Antibody TherapyMusNewly DiagnosedNormal CellPancreasPathway interactionsPatientsPharmaceutical PreparationsPhasePhase I Clinical TrialsPhase II Clinical TrialsPlayPredispositionPrimatesProductionProgress ReportsPropertyProteomicsProtocols documentationPublic HealthQuality ControlRNA HelicaseRadiationRadiation therapyRadiation-Sensitizing AgentsReagentRecruitment ActivityRegimenRegulationReportingReproduction sporesResearchResistanceRoleScienceSignal TransductionSiteStagingTNFRSF10A geneTNFSF10 geneTailTechnologyTestingTherapeuticTherapeutic AgentsTissue SampleTissuesToxic effectToxicologyTranslatingTranslational ResearchTranslationsTreatment EfficacyTreatment ProtocolsTumor Cell LineUniversitiesUniversity of Alabama at Birmingham Cancer CenterUniversity of Minnesota Cancer CenterXenograft ModelXenograft procedureabstractingassay developmentbasecancer cellcancer therapychemotherapeutic agentchemotherapyclinical efficacycytotoxicitydocetaxeldrug developmentgemcitabinein vivoindustry partnerinhibitor/antagonistirinotecanmalignant breast neoplasmneoplastic cellnovelnovel therapeuticsoxaliplatinpancreas xenograftpancreatic neoplasmpatient populationpre-clinicalpreclinical studyprogramsprotein complexreceptorresponsesmall moleculesynergismtherapeutic targettreatment strategytrendtumortumor immunology
中文摘要
项目总结(见说明书);
英文摘要
PROJECT SUMMARY (See instructions);
This proposal is a continuation of Project 2 in the original SPORE grant. Pertinent to this proposal, we have
developed an anti-DRS monoclonal antibody therapy for pancreatic cancer through in vitro studies, animal
model efficacy and with an industry partner (Daiichi Sankyo), Phase I and recently completed Phase II trials
in pancreatic cancer. We have also discovered a novel molecule (DDX3) which appears to play a major role
in regulation of anti-DRS mediated apoptosis. In this proposal, we will explore two strategies to enhance the
efficacy of anti-DRS monoclonal therapy especially in pancreatic tumor cell lines which are intermediate or
resistant to anti-DRS. The two strategies are to evaluate the addition of a monoclonal anti-DR4 reagent or
the addition of small molecule modulators ofthe apoptosis cascade. The two apoptosis modulators to be
evaluated are AT-101, a Bcl-2 family inhibitor, and AT-406, an lAP family inhibitor. These two strategies will
be studied using in vitro analysis and orthotopic and metastatic xenogeneic pancreatic cancer models
leading to a Phase I trial of the best strategy. In addition, we will continue studies of DDX3 and the
DRS/DDX3 complex as a putative biomarker for tumor cell sensitivity/resistance to death receptor mediated
anti-tumor efficacy and as the target of enhancement strategies for anti-DR mediated anti-tumor effects.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Therapy of pancreatic cancer with 212Pb-labeled B7-H3 specific Ab and LDE225
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批准号:8637541
-
项目类别:
-
资助金额:$18.6万
-
财政年份:2014
-
负责人:DONALD J. BUCHSBAUM
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依托单位:
Career Development Program
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批准号:7962166
-
项目类别:
-
资助金额:$21.76万
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财政年份:2010
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负责人:DONALD J. BUCHSBAUM
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依托单位:
Administrative Core
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批准号:7962142
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项目类别:
-
资助金额:$12.64万
-
财政年份:2010
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负责人:DONALD J. BUCHSBAUM
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依托单位:
Developmental Research Program
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批准号:7962164
-
项目类别:
-
资助金额:$8.57万
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财政年份:2010
-
负责人:DONALD J. BUCHSBAUM
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依托单位:
UAB / UMN SPORE in Pancreatic Cancer
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批准号:8131055
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项目类别:
-
资助金额:$218.5万
-
财政年份:2003
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负责人:DONALD J. BUCHSBAUM
-
依托单位:
UAB / UMN SPORE in Pancreatic Cancer
-
批准号:8528346
-
项目类别:
-
资助金额:$215.05万
-
财政年份:2003
-
负责人:DONALD J. BUCHSBAUM
-
依托单位:
UAB / UMN SPORE in Pancreatic Cancer
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批准号:7939097
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项目类别:
-
资助金额:$230.0万
-
财政年份:2003
-
负责人:DONALD J. BUCHSBAUM
-
依托单位:
SPORE in Pancreatic Cancer
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批准号:7287817
-
项目类别:
-
资助金额:$85.56万
-
财政年份:2003
-
负责人:DONALD J. BUCHSBAUM
-
依托单位:
UAB / UMN SPORE in Pancreatic Cancer
-
批准号:8707193
-
项目类别:
-
资助金额:$216.2万
-
财政年份:2003
-
负责人:DONALD J. BUCHSBAUM
-
依托单位:
SPORE in Pancreatic Cancer
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批准号:7090644
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项目类别:
-
资助金额:$88.11万
-
财政年份:2003
-
负责人:DONALD J. BUCHSBAUM
-
依托单位:
UAB / UMN SPORE in Pancreatic Cancer
-
批准号:8277122
-
项目类别:
-
资助金额:$230.0万
-
财政年份:2003
-
负责人:DONALD J. BUCHSBAUM
-
依托单位:
EVALUATION OF CH2 DELETED HUCC49 FOR INTRAPERITONEAL RIT
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批准号:6376847
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项目类别:
-
资助金额:$22.68万
-
财政年份:1999
-
负责人:DONALD J. BUCHSBAUM
-
依托单位:
EVALUATION OF CH2 DELETED HUCC49 FOR INTRAPERITONEAL RIT
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批准号:2856503
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项目类别:
-
资助金额:$22.74万
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财政年份:1999
-
负责人:DONALD J. BUCHSBAUM
-
依托单位:
EVALUATION OF CH2 DELETED HUCC49 FOR INTRAPERITONEAL RIT
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批准号:6174021
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项目类别:
-
资助金额:$22.18万
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财政年份:1999
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负责人:DONALD J. BUCHSBAUM
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依托单位:
GENETIC RADIOIMMUNOTHERAPY OF PANCREATIC CANCER
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批准号:6137597
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项目类别:
-
资助金额:$21.22万
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财政年份:1998
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负责人:DONALD J. BUCHSBAUM
-
依托单位:
GENETIC RADIOIMMUNOTHERAPY OF PANCREATIC CANCER
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批准号:2856453
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项目类别:
-
资助金额:$20.69万
-
财政年份:1998
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负责人:DONALD J. BUCHSBAUM
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依托单位:
GENETIC RADIOIMMUNOTHERAPY OF PANCREATIC CANCER
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批准号:2488567
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项目类别:
-
资助金额:$20.17万
-
财政年份:1998
-
负责人:DONALD J. BUCHSBAUM
-
依托单位:
01 Inflammation, Immunology and Immunotherapeutics Program
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批准号:10362795
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项目类别:
-
资助金额:$2.66万
-
财政年份:1997
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负责人:DONALD J. BUCHSBAUM
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依托单位:
NEW BCAS FOR RADIOIMMUNOTHERAPY WITH RADIOMETALS
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批准号:6376044
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项目类别:
-
资助金额:$25.91万
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财政年份:1996
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负责人:DONALD J. BUCHSBAUM
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依托单位:
NEW BCAS FOR RADIOIMMUNOTHERAPY WITH RADIOMETALS
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批准号:2909189
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项目类别:
-
资助金额:$25.79万
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财政年份:1996
-
负责人:DONALD J. BUCHSBAUM
-
依托单位: